Real-world study on characteristics of advanced melanoma patients with sustained complete response (CR) after elective 1<sup>st</sup> line anti-programmed death-1 (anti-PD1) monotherapy discontinuation.
Authors: Sebastian Ochenduszko, Javier García, María Jose Juan-Fita, Ines Gonzalez-Barrallo, Julio Herrero Colomina, Robert Diaz Beveridge, Silverio Ros Martinez, Blanca Sanchez Lafuente, Alberto Jacobo Cunquero Tomas, Alfonso Berrocal, Pablo Cerezuela-Fuentes, Pablo Luna Fra, Alicia Gervás Peeters, José Luis Sanchez Gonzalez, Andres Meana Garcia, Mariasun Algarra Garcia, Eugenio Palomares García, Javier Perez Altozano, Mónica Tallón Guerola, Inmaculada Maestu
Journal: Journal of Clinical Oncology (2022)

e21529 Background: Previous reports proved the feasibility of immunotherapy (IT) discontinuation in advanced melanoma (MEL) patients (pts) in case of CR. We aimed to investigate clinical characteristics of pts with sustained CR after elective discontinuation of the 1 st line anti-PD1 monotherapy in the real world setting. Methods: This is a multicenter retrospective cohort study. Eligible pts ≥ 18 years with unresectable locally advanced or metastatic primary cutaneous (PC) or unknown primary (UP) MEL with at least one measurable lesion per RECIST version 1.1 at baseline, treated with nivolumab (NIVO) o pembrolizumab (PEMBRO) monotherapy with no previous IT were included. All pts achieved CR to the treatment confirmed by computed tomography (CT) or positron emission tomography (PET-CT) and had at least one imaging study in the follow-up (FU). IT discontinuation was at the discretion of the treating physician. Pts with CR who stopped IT due to toxicity grade (G) 3 and/or 4 were excluded. Information regarding baseline characteristics, survival and immune related adverse events (irAEs) was obtained from patients´ charts. Data cut-off was February 10 th 2022. Results: 36 pts treated in 12 hospitals in Spain between October 8 th 2015 and October 27 th 2021 were identified. Mean age was 66.8 years and mean BMI was 27.4. Twenty eight (77.8%) pts were males and 35 (97.2%) had ECOG PS 0-1. PC melanoma was observed in 33 (91.7%) pts, UP in 3 (8.3%). 35 pts (97.2%) had metastatic disease, with 11 (30.6%) pts with ≥3 metastatic sites. There were 21 (58.4%) pts with stage M1a-M1b disease; only 3 (8.3%) had liver and 2 (5.6%) had brain metastases. Baseline LDH was within normal limits in 28 (77.8%) pts and 31 (86.1%) pts had baseline neutrophil to lymphocyte ratio ≤3. Treatment received: PEMBRO 21 (58.3%), NIVO 15 (41.7%) pts. CR to treatment was confirmed by PET-CT in 27 (75.0%) pts. Median duration of anti-PD1 IT was 23.5 months (range 1.3 - 50.5) and median time to CR was 12.0 months (range 2.2 - 50.2). With the median FU time off treatment of 24.1 months (95% CI 19.4 – 28.8), median progression free survival (PFS) after IT discontinuation has not been reached: estimated PFS at 1 and 2 years were 94.1% and 89.2%, respectively. Estimated overall survival from start of IT at 3 and 4 years were 97.2% and 93.5%, respectively. irAEs G 1-2 were observed in 30 (83.3%) pts and the most common were: vitiligo 8 (22.2%), pruritis 4 (11.1%), other skin toxicity 8 (22.2%), hypothyroidism 5 (13.9%), pneumonitis 3 (8.3%), colitis 5 (13.9%), hepatitis 3 (8.3%), arthralgia 5 (13.9%) and nephritis 3 (8.3%). Conclusions: Our study confirms sustained CR after elective 1 st line anti-PD1 monotherapy discontinuation in a cohort of advanced PC and UP MEL pts with favorable established prognostic factors for MEL at baseline. Frequency of irAEs was concordant with previous reports on IT.